Senescence (a state of cell cycle arrest) has been explored by biologists and clinicians alike as a therapeutic intervention for cancer. Senescence is a naturally encoded feature of the human body essential for healing and regeneration. Cells with defects become senescent and release the senescence associated secretory proteome that involves cytokines, interleukins, growth factors etc. SASP is responsible for attracting immune cells for senescent cell clearance. Senescence, however, plays a dual role in  tumor progression. While cell cycle arrest does inhibit tumor growth, these senescent cells remain metabolically active and produce SASP that promotes inflammation, healing, angiogenesis, metastasis etc. Thus, it acts like a dual-edged sword.

TNBC Ranjini
Dual edged nature of senescent cells

We try to understand how senescent cells modify the tumor microenvironment of triple-negative breast cancer using a hybrid experimental and theoretical approach. We first track the density and frequency of senescent cells in vitro using the senescence-associated beta-galactosidase assay and microscopy. We use this data to generate a frequency-based selection model inspired by the Lotka Volterra Equations. We find the senescent cells oscillate about a mean frequency, in vitro, and have higher fitness in drug-treated culture. We also show that the condition media from these cells is able to re-establish the same dynamics in untreated cells. We further hypothesise that there is an overlap between the stemness oriented reprogramming and stemness. Indeed using the sphere assay we are able to show a high correlation between cancer stem cell formation efficiency and senescence.

Our next milestone is to decipher the interactions of senescent cells with stromal cells.

 

PI
Dr. Anindita Chakrabarty and Dr. Sudeepto Bhattacharya
Place
Shiv Nadar University, India
Project Duration
May 2018 Onwards